A repurposed liver medicine enters a major Parkinson’s test
Ursodeoxycholic acid, or UDCA, has been added to the Edmond J Safra Accelerating Clinical Trials in Parkinson’s Disease trial, a platform designed to test several possible disease-modifying treatments in parallel. The move takes a drug already used for certain liver conditions into a much larger effort to determine whether it can slow the progression of Parkinson’s disease.
Researchers at the University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust identified UDCA as a candidate after screening an entire drug library in tissue samples from people with Parkinson’s disease. The work focused on mitochondrial function, an area of biology increasingly central to efforts to understand why dopamine-producing nerve cells fail in the disease.
Why mitochondria are the focus
Mitochondria are often described as cells’ power plants because they help produce the energy cells need to function. In Parkinson’s disease, the loss of mitochondrial function in dopamine-producing nerve cells in a movement-controlling part of the brain is believed to play an important role in disease progression.
The Sheffield researchers found that UDCA showed considerable promise for improving mitochondrial function in Parkinson’s disease. Their hypothesis is that protecting vulnerable nerve cells from this form of cellular malfunction could help slow progression. That remains a hypothesis to be tested: the drug’s addition to the larger trial is intended to establish whether the biological promise translates into a meaningful clinical effect.
Testing several candidates at once
UDCA is the third active treatment arm in the EJS ACT-PD study. Telmisartan and terazosin were already being tested against placebo, and the platform’s structure is meant to accelerate the search for effective therapies by assessing multiple candidates more efficiently than conventional one-drug-at-a-time trials.
That matters in Parkinson’s research because the condition is currently relentlessly progressive, while many available treatments are directed at managing symptoms rather than changing the disease’s underlying course. A trial that can bring several plausible candidates into a shared testing framework may shorten the time needed to identify treatments worth advancing and to rule out those that do not deliver benefit.
For UDCA, the case for proceeding rests on more than its laboratory screening results. The medicine has been used for certain liver conditions for more than 30 years, giving researchers an established history of clinical use in another setting. It was also found to be safe and well tolerated in people with Parkinson’s disease in the early-stage UP study.
Safety is not proof of effectiveness
The earlier safety findings are important, but they do not show that UDCA slows Parkinson’s disease. Large-scale testing is now required to assess effectiveness. The EJS ACT-PD trial is the next step in separating a promising repurposing lead from a treatment that can demonstrably alter outcomes for patients.
Repurposing an established medicine can be attractive because a drug’s previous use may provide useful information about tolerability and practical administration. But Parkinson’s is a distinct clinical setting, and evidence that a drug is tolerated does not establish that it protects dopamine-producing cells or changes the pace of decline. The placebo comparison in the trial is therefore central to the program.
An important milestone, not a result
The addition of UDCA is a milestone for both the drug and the multidrug trial platform. It reflects a chain of work from patient-tissue screening, through early testing in people with Parkinson’s disease, to selection for a larger study. It also adds another approach to a program intended to search more quickly for disease-modifying treatments.
The decisive question is still ahead: whether improved mitochondrial function associated with UDCA can produce a measurable slowing of Parkinson’s progression. Until the trial reports, the development is best understood as a well-supported candidate entering a consequential test, rather than evidence that a new treatment has already been established.
This article is based on reporting by Medical Xpress. Read the original article.
Originally published on medicalxpress.com
